BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome.
BLOC-1
BLOC1S5
Hermansky–Pudlak syndrome
albinism
pathogenic variant
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
04
05
2020
accepted:
04
06
2020
revised:
03
06
2020
pubmed:
23
6
2020
medline:
28
4
2021
entrez:
23
6
2020
Statut:
ppublish
Résumé
Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, excessive bleeding, and often additional symptoms. Variants in ten different genes have been involved in HPS. However, some patients lack variants in these genes. We aimed to identify new genes involved in nonsyndromic or syndromic forms of albinism. Two hundred thirty albinism patients lacking a molecular diagnosis of albinism were screened for pathogenic variants in candidate genes with known links to pigmentation or HPS pathophysiology. We identified two unrelated patients with distinct homozygous variants of the BLOC1S5 gene. Patients had mild oculocutaneous albinism, moderate bleeding diathesis, platelet aggregation deficit, and a dramatically decreased number of platelet dense granules, all signs compatible with HPS. Functional tests performed on platelets of one patient displayed an absence of the obligate multisubunit complex BLOC-1, showing that the variant disrupts BLOC1S5 function and impairs BLOC-1 assembly. Expression of the patient-derived BLOC1S5 deletion in nonpigmented murine Bloc1s5 Mutation of BLOC1S5 is disease-causing, and we propose that BLOC1S5 is the gene for a new form of Hermansky-Pudlak syndrome, HPS-11.
Identifiants
pubmed: 32565547
doi: 10.1038/s41436-020-0867-5
pii: S1098-3600(21)00754-1
pmc: PMC7529931
mid: NIHMS1609960
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1613-1622Subventions
Organisme : NEI NIH HHS
ID : R01 EY015625
Pays : United States
Commentaires et corrections
Type : CommentIn
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